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Isolated Perfused Porcine Skin Flap Systems

  • Jim E. Riviere
Part of the Pharmaceutical Biotechnology book series (PBIO, volume 8)

Abstract

The ultimate goal of an in vitro model system is to predict the behavior of the drug in the in vivo setting. Most in vitro skin models used to assess the percutaneous absorption or transdermal delivery of topically applied drugs are designed around the assumption that the stratum corneum and/or epidermis is the principal barrier to compound penetration through skin. Thus, all such models were usually avascular and, until recently, nonviable preparations. However, in vivo, this stratum corneum and living epidermal barrier resides on a well-vascularized and metabolically active dermal substrate offering ample biological targets for specific types of drugs. Drugs may be vasoactive and modulate the cutaneous microcirculation; they may serve as substrates of epidermal and dermal drug-metabolizing enzymes, or they may activate cytokine and/or other modulator receptors which result in changes in epidermal, dermal, or endothelial cell function. Therefore, the anatomical and physiological complexity of human skin is significantly greater than that modeled in existing in vitro systems, which thus do not afford the possibility of detecting these potential biologically relevant events.

Keywords

Stratum Corneum Pharmacokinetic Model Skin Flap Luteinizing Hormone Release Hormone Percutaneous Absorption 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Behrendt, H., and Kampffmeyer, H. G., 1989, Absorption and ester cleavage of methyl salicylate by skin of single-pass perfused rabbit ears, Xenobiotica 19:131–141.PubMedCrossRefGoogle Scholar
  2. Bowman, K. F., Montero-Riviere, N. A., and Riviere, J. E., 1991, Development of surgical techniques for preparation of in vitro isolated perfused porcine skin flaps for percutaneous absorption studies, Am. J. Vet. Res. 25:75–82.Google Scholar
  3. Carver, M. P., Williams, P. L., and Riviere, J. E., 1989, The isolated perfused porcine skin flap (IPPSF). III. Percutaneous absorption pharmacokinetics of organophosphates, steroids, benzoic acid and caffeine, Toxicol. Appl. Pharmacol. 97:324–337.PubMedCrossRefGoogle Scholar
  4. Carver, M. P., Levi, P. E., and Riviere, J. E., 1990, Parathion metabolism during percutaneous absorption in perfused porcine skin. Pestic. Biochem. Physiol. 38:245–254.CrossRefGoogle Scholar
  5. Celesti, L., Murratzu, C., Valoti, M., Sgaragli, G., and Corti, P., 1993, The single-pass perfused rabbit ear as a model for studying percutaneous absorption of clonazepam, Methods Find. Exp. Clin. Pharmacol. 15:49–56.PubMedGoogle Scholar
  6. Chang, S. K., and Riviere, J. E., 1991, Percutaneous absorption of parathion in vitro in porcine skin. Effects of dose, temperature, humidity and perfusate composition on absorptive flux, Fundam. Appl. Toxicol. 17:494–504.PubMedCrossRefGoogle Scholar
  7. Chang, S. K., and Riviere, J. E., 1993, Effect of humidity and occlusion on the percutaneous absorption of parathion in vitro, Pharm. Res. 10:152–155.PubMedCrossRefGoogle Scholar
  8. Chang, S. K., Dauterman, W. C., and Riviere, J. E., 1994a, Percutaneous absorption of parathion and its metabolites paraoxon and p-nitrophenol administered alone or in combination: in vitro flow through diffusion cell system, Pestic. Biochem. Physiol. 48:56–62.CrossRefGoogle Scholar
  9. Chang, S. K., Williams, P. L., Dauterman, W. C., and Riviere, J. E., 1994b, Percutaneous absorption, dermatopharmacokinetics, and related biotransformation studies of carbaryl, lindane, malathion and parathion in isolated perfused porcine skin, Toxicology 91:269–280.PubMedCrossRefGoogle Scholar
  10. de Lange, J., van Eck, P., Elliott, G. R., de Kort, W. L. A. M., and Wolthius, O. L., 1992, The isolated blood-perfused pig ear: An inexpensive and animal saving model for skin penetration studies, J. Pharmacol. Toxicol. Methods 27:71–77.PubMedCrossRefGoogle Scholar
  11. Feldberg, W., and Paton, W. D. M., 1951, Release of histamine from skin and muscle in the cat by opium alkaloids and other histamine liberators, J. Physiol. 114:490–509.PubMedGoogle Scholar
  12. Heit, M., Williams, P., Jayes, F. L., Chang, S. K., and Riviere, J. E., 1993, Transdermal iontophoretic peptide delivery. in vitro and in vivo studies with luteinizing hormone releasing hormone (LHRH), J. Pharm. Sci. 82:240–243.PubMedCrossRefGoogle Scholar
  13. Hiernickel, H., 1985, An improved method for in vitro perfusion of human skin, Br. J. Dermatol. 112: 299–305.PubMedCrossRefGoogle Scholar
  14. Kietzmann, M., Arens, D., Loscher, W., and Lubach, D., 1991, Studies on the percutaneous absorption of dexamethasone using a new in vitro model, the isolated perfused bovine udder, in: Prediction of Percutaneous Penetration (R. C. Scott, R. H. Guy, J. Hadgraft, and H. E. Bodee, eds.), IBC Technical Services, Ltd., London, pp. 519–526.Google Scholar
  15. Kjaersgaard, A. R., 1954, Perfusion of isolated dog skin, J. Invest. Dermatol. 22:135–141.PubMedGoogle Scholar
  16. Kreidstein, M. L., Pang, C. Y., Levine, R. H., and Knowlton, R. J., 1991, The isolated perfused human skin flap: Design, perfusion technique, metabolism and vascular reactivity, Plast. Reconstr. Surg. 87: 741–749.PubMedCrossRefGoogle Scholar
  17. Monteiro-Riviere, N. A., 1990. Specialized technique: The isolated perfused porcine skin flap (IPPSF), in: Methods for Skin Absorption (B. W. Kemppainen and W. G. Reifenrath, eds.), CRC Press, Boca Raton, Florida, pp. 175–189.Google Scholar
  18. Monteiro-Riviere, N. A., 1992, Use of isolated perfused skin model in dermatotoxicology, In Vitro Toxicol. 5:219–233.Google Scholar
  19. Monteiro-Riviere, N. A., Bowman, K. F., Scheidt, V. J., and Riviere, J. E., 1987, The isolated perfused porcine skin flap (IPPSF): II. Ultrastructural and histological characterization of epidermal viability, in vitro Toxicol. 1:241–252.Google Scholar
  20. Monteiro-Riviere, N. A., Bristol, D. G., Manning, T. O., Rogers, R. A., and Riviere, J. E., 1990, Interspecies and interregional analysis of the comparativc histological thickness and laser Doppler blood flow measurements at five cutaneous sites in nine species, J. Invest. Dermatol. 95:582–586.PubMedCrossRefGoogle Scholar
  21. Monteiro-Riviere, N. A., Inman, A. O., and Riviere, J. E., 1994, Development and characterization of a novel skin model for phototoxicology, Photodermatol, Photoimmunol. Photomed. 11:235–243.Google Scholar
  22. Qiao, G. L., and Riviere, J. E., 1995, Significant effects of application site and occlusion on the pharmacokinetics of cutaneous penetration and biotransformation of parathion in vivo in swine, J. Pharm. Sci. 84:425–432.PubMedCrossRefGoogle Scholar
  23. Qiao, G. L., Williams, P. L., and Riviere, J. E., 1994, Percutaneous absorption, biotransformation and systemic disposition of parathion in vivo in swine. I. Comprehensive pharmacokinetic model, Drug Metab. Dispos. 22:459–471.PubMedGoogle Scholar
  24. Riviere, J. E., and Chang, S., 1992, Transdermal penetration and metabolism of organophosphate insecticides, in: Organophosphates: Chemistry, Fate and Effects (J. E. Chambers and P. L. Levi, eds.), Academic Press, New York, pp. 241–253.Google Scholar
  25. Riviere, J. E., and Monteiro-Riviere, N. A., 1991, The isolated perfused porcine skin flap as an in vitro model for percutaneous absorption and cutaneous toxicology, Crit. Rev. Toxicol. 21:329–344.PubMedCrossRefGoogle Scholar
  26. Riviere, J. E., and Williams, P. L., 1992, Pharmacokinetic implications of changing blood flow in skin, J. Pharm. Sci. 81:601–602.PubMedCrossRefGoogle Scholar
  27. Riviere, J. E., Bowman, K. F., Monteiro-Riviere, N. A., Carver, M. P., and Dix, L. P., 1986, The isolated perfused porcine skin flap (IPPSF). I. A novel in vitro model for percutaneous absorption and cutaneous toxicology studies, Fundam. Appl. Toxicol. 7:444–453.PubMedCrossRefGoogle Scholar
  28. Riviere, J. E., Sage, B. S., and Williams, P. L., 1991, The effects of vasoactive drugs on transdermal lidocaine iontophoresis, J. Pharm. Sci. 80:615–620.PubMedCrossRefGoogle Scholar
  29. Riviere, J. E., Monteiro-Riviere, N. A., and Inman, A. O., 1992a, Determination of lidocaine concentration in skin after transdermal iontophoresis: Effects of vasoactive drugs, Pharm. Res. 9:211–214.PubMedCrossRefGoogle Scholar
  30. Riviere, J. E., Williams, P. L., Hillman, R., and Mishky, L., 1992b, Quantitative prediction of transdermal iontophoretic delivery of arbutamine in humans using the in vitro isolated perfused porcine skin flap (IPPSF), J. Pharm. Sci. 81:504–507.PubMedCrossRefGoogle Scholar
  31. Rogers, R. A., and Riviere, J. E., 1994, Pharmacologic modulation of cutaneous vascular resistance in the isolated perfused porcine skin flap (IPPSF), J. Pharm. Sci. 83:1682–1689.PubMedCrossRefGoogle Scholar
  32. Srikrishna, V., Riviere, J. E., and Monteiro-Riviere, N. A., 1992, Cutaneous toxicity and absorption of paraquat in porcine skin, Toxicol. Appl. Pharmacol. 115:89–97.PubMedCrossRefGoogle Scholar
  33. Vaden, S. L., Page, R. L., Peters, B. P., Cline, J. M., and Riviere, J. E., 1993, Development and characterization of an isolated and perfused tumor and skin preparation for evaluation of drug disposition, Cancer Res. 53:101–105.PubMedGoogle Scholar
  34. Williams, P. L., and Riviere, J. E., 1989a, Definition of a physiologic pharmacokinetic model of cutaneous drug distribution using the isolated perfused porcine skin flap (IPPSF), J. Pharm. Sci. 78:550–555.PubMedCrossRefGoogle Scholar
  35. Williams, P. L., and Riviere, J. E., 1989b, Estimation of physiological volumes in the isolated perfused porcine skin flap, Res. Commun. Chem. Pathol. Pharmacol. 66:145–158.PubMedGoogle Scholar
  36. Williams, P. L., and Riviere, J. E., 1993, A model describing transdermal iontophoretic delivery of lidocaine incorporating consideration of cutaneous microvascular state, J. Pharm. Sci. 82:1080–1084.PubMedCrossRefGoogle Scholar
  37. Williams, P. L., and Riviere, J. E., 1994, A “full-space” method for predicting in vivo transdermal plasma drug profiles reflecting both cutaneous and systemic variability, J. Pharm. Sci. 83:1062–1064.PubMedCrossRefGoogle Scholar
  38. Williams, P. L., and Riviere, J. E., 1995, A biophysically-based dermatopharmacokinetic compartment model for quantifying percutaneous penetration and absorption of topically applied agents. I. Theory, J. Pharm. Sci. 84:599–608.PubMedCrossRefGoogle Scholar
  39. Williams, P. L., Carver, M. P., and Riviere, J. E., 1990, A physiologically relevant pharmacokinetic model of xenobiotic percutaneous absorption utilizing the isolated perfused porcine skin flap (IPPSF), J. Pharm. Sci. 79:305–311.PubMedCrossRefGoogle Scholar
  40. Williams, P. L., Brooks, J. D., Inman, A. I., Monteiro-Riviere, N. A., and Riviere, J. E., 1994, Determination of physicochemical properties of phenol, paranitrophenol, acetone and ethanol relevant to quantitating their percutaneous absorption in porcine skin, Res. Commun. Chem. Pathol. Pharmacol. 83:61–75.PubMedGoogle Scholar
  41. Zhang, A., Riviere, J. E., and Monteiro-Riviere, N. A., 1995a, Evaluation of protective effects of sodium thiosulfate, cysteine, niacinamide and indomethacin on sulfur mustard-treated isolated perfused porcine skin, Chem.-Biol. Interact. 96:249–262.PubMedCrossRefGoogle Scholar
  42. Zhang, A., Riviere, J. E., and Monteiro-Riviere, N. A., 1995b, Topical sulfur mustard induces changes in prostaglandins and interleukin la in isolated perfused porcine skin, In Vitro Toxicol. 8:149–158.Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Jim E. Riviere
    • 1
  1. 1.Cutaneous Pharmacology and Toxicology CenterNorth Carolina State UniversityRaleighUSA

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